Cell Free Expression of hif1α and p21 in Maternal Peripheral Blood as a Marker for Preeclampsia and Fetal Growth Restriction

Preeclampsia, a severe unpredictable complication of pregnancy, occurs in 6% of pregnancies, usually in the second or third trimester. The specific etiology of preeclampsia remains unclear, although the pathophysiological hallmark of this condition appears to be an inadequate blood supply to the placenta. As a result of the impaired placental blood flow, intrauterine growth restriction (IUGR) and consequential fetal oxidative stress may occur. Consistent with this view, pregnancies complicated by preeclampsia and IUGR are characterized by up-regulation of key transcriptional regulators of the hypoxic response including, hif1α and as well as p53 and its target genes. Recently, the presence of circulating cell-free fetal RNA has been documented in maternal plasma. We speculated that pregnancies complicated by preeclampsia and IUGR, will be associated with an abnormal expression of p53 and/or hif1α related genes in the maternal plasma. Maternal plasma from 113 singleton pregnancies (72 normal and 41 complicated pregnancies) and 19 twins (9 normal and 10 complicated pregnancies) were collected and cell free RNA was extracted. The expression of 18 genes was measured by one step real-time RT-PCR and was analyzed for prevalence of positive/negative expression levels. Results indicate that, among the genes examined, cell free plasma expressions of p21 and hif1α were more prevalent in pregnancies complicated by hypoxia and/or IUGR (p<0.001). To conclude, we present in this manuscript data to support the association between two possible surrogate markers of hypoxia and common complications of pregnancy. More work is needed in order to implement these findings in clinical practice

A meta-analysis of previous falls and subsequent fracture risk in cohort studies

NC Harvey acknowledges funding from the UK Medical Research Council (MC_PC_21003; MC_PC_21001). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Funding for the MrOS USA study comes from the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. Funding for the SOF study comes from the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), supported by grants (AG05407, AR35582, AG05394, AR35584, and AR35583). Funding for the Health ABC study was from the Intramural research program at the National Institute on Aging under the following contract numbers: NO1-AG-6–2101, NO1-AG-6–2103, and NO1-AG-6–2106.Peer reviewedPostprin

Managing Osteoporosis: A Survey of Knowledge, Attitudes and Practices among Primary Care Physicians in Israel

<div><p>Background</p><p>Osteoporosis is a systemic skeletal disorder characterized by impaired bone quality and microstructural deterioration leading to an increased propensity to fractures. This is a major health problem for older adults, which comprise an increasingly greater proportion of the general population. Due to a large number of patients and the insufficient availability of specialists in Israel and worldwide, osteoporosis is treated in large part by primary care physicians. We assessed the knowledge of primary care physicians on the diagnosis and treatment of osteoporosis.</p><p>Methods</p><p>Physician's knowledge, sources of knowledge acquisition and self-evaluation of knowledge were assessed using a multiple choice questionnaire. Professional and demographic characteristics were assessed as well.</p><p>Results</p><p>Of 490 physicians attending a conference, 363 filled the questionnaires (74% response rate). The physicians demonstrated better expertise in diagnosis than in medications (mechanism of action, side effects or contra-indications) but less than for other treatment related decisions. Overall, 50% demonstrated adequate knowledge of calcium and vitamin D supplementation, 51% were aware of the main therapeutic purpose of osteoporosis pharmacotherapy and 3% were aware that bisphosphonates should be avoided in patients with impaired renal function. Respondents stated frontal lectures at meetings as their main source of information on the subject.</p><p>Conclusion</p><p>The study indicates the need to intensify efforts to improve the knowledge of primary care physicians regarding osteoporosis, in general; and osteoporosis pharmacotherapy, in particular.</p></div

Summary of survey results: knowledge of primary care physicians on the diagnosis and treatment of osteoporosis (n = 363).

<p>Summary of survey results: knowledge of primary care physicians on the diagnosis and treatment of osteoporosis (n = 363).</p

Professional status, age and seniority (number of years in practice) of participating physicians.

<p>Professional status, age and seniority (number of years in practice) of participating physicians.</p

The proximity of the date of physicians' participation in lectures on osteoporosis.

<p>The proximity of the date of physicians' participation in lectures on osteoporosis.</p

Exposure to alendronate is associated with a lower risk of bone metastases in osteoporotic women with early breast cancer

Background: Bisphosphonate (BP) treatment to prevent bone loss in breast cancer patients is already well established. However, data on the association between oral BP exposure before cancer diagnosis and disease outcomes in patients with early breast cancer are still scarce. Limited information is available on alendronate, the most common oral agent for the treatment of post-menopausal osteoporosis, regarding the association with bone metastases. Aim: To examine the association between oral bisphosphonate exposure before cancer diagnosis and the risk of bone metastases in osteoporotic women diagnosed with early breast cancer. Subjects and methods: This historical cohort study was conducted at the oncology division at Tel Aviv Medical Center. The study population included post-menopausal women with early breast cancer, diagnosed between 2002 and 2012. Data on cancer characteristics, diagnosis of osteoporosis, prior bisphosphonate exposure and outcome were collected from medical files. Results: Among 297 osteoporotic women identified, 145 (49%) were treated with bisphosphonates (alendronate in 90% of the cases) before cancer diagnosis. BP-treated women were significantly older than the BP-naïve ones (67.9 years vs 64.6 years, p = 0.01), but comparable in risk factors and disease characteristics. Over a mean follow up of 5.6 years, nine cases of bone metastases were identified, eight of them among BP-naïve patient (cumulative incidence of 9.9%) and one among BP-treated patients (0.7%). In a multivariable Cox's proportional hazards survival model the use of BP prior to cancer diagnosis was associated with a hazard ratio of 0.04 (95%CI:0.004–0.403, p = 0.006) for bone metastasis. The HR remained similar after further adjustment for tumor stage and cancer therapy. Conclusions: History of alendronate use is associated with a lower likelihood of bone metastases in postmenopausal women with early breast cancer. Oral bisphosphonate treatment could be sufficient for reducing the risk of bone metastases. Keywords: Bisphosphonates, Alendronate, Breast cancer, Bone metastase

Role of Side Effects, Physician Involvement, and Patient Perception in Non-Adherence with Oral Bisphosphonates

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s12325-016-0360-3">https://link.springer.com/article/10.1007/s12325-016-0360-3</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p